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CCSVI research: Why are the results so different?

There are many components to a "good" experiment - not just that a researcher gets the results that he or she wants, showing that their hypothesis was valid with statistical significance. A very important part of scientific "success" is that the experiment is reproducible, meaning that a scientist anywhere who followed the protocol exactly should be fairly certain to get the same results (or at least very close).

Trying to establish a correlation between chronic cerebrospinal venous insufficiency (CCSVI) and multiple sclerosis (MS) has been a huge scientific mess, with results ranging from 0% correlation of the presence of CCSVI in people with MS to 100% of people with MS having these deformities or "stenosis" of the veins that drain blood from the brain. A presentation by Dr. Doepp pointed out that CCSVI results were often difficult to reproduce in the same patient, even using the same imaging equipment and techniques.

This difference in the correlations found by different scientists indicates that there is a problem with the way the test is being done in various people in various places. Using different types of imaging technology on different sections of the veins can easily give vastly different results in the research. Other factors can also come into play.

According to Robert Fox, of the Mellen Clinic of the Cleveland Clinic, one easily-overlooked challenge in getting an accurate image of the veins in people with MS is hydration. Because many people with MS have bladder dysfunction that either leads to incontinence or urgency, they may be chronically dehydrated, as they reduce fluid intake to avoid accidents. I have also read of people whose results were considered "invalid" or "unusable" because their head was tilted a couple degrees in the wrong direction.

Dr. Fox and his research group found a way around the measurement error that can be introduced with these advanced imaging technologies and patient behavior – he took a real look at the veins of people that had died and donated their bodies to research.

The group "harvested" the internal jugular (IJV), subclavian, brachiocephalic, and azygous (AZY) veins from 7 people with MS and 6 people without MS. These veins were prepared by injecting them with silicone, then cut open and mounted for examination. They defined "stenosis" as a reduction of more than 50% of the inner diameter of the veins, as compared to a normal region in the same vein.

The group found a variety of abnormalities in the veins they examined which could have affected blood flow. However, these abnormalities were found in both people with MS and the people without MS (4 of 7 MS patients and 3 of 6 controls). However, there were differences in the valves and other structures, like flaps or membranes, within the veins in more of the people with MS (6 out of 7) than in the people without MS (2 out of 6), all of which could impair blood flow. These structures could very well create a stenosis (blockage) without there being a difference in thickness of vein walls.

This tells us two things: 1) these abnormal structures are very delicate, meaning some of these abnormalities would probably be missed with certain imaging techniques, such as magnetic resonance venography, indicating that Doppler ultrasound might be better; 2) we need to look at more than just the thickness of the vein walls, as there may be abnormalities inside the veins that could provide an important part of the puzzle.

Julie Stachowiak, PhD

Julie is the author of the Multiple Sclerosis Manifesto, the winner of the 2009 ForeWord Book of the Year Award in the Health Category. She is an epidemiologist who is also a person living with MS, Julie has an in-depth understanding about current research and scientific developments around MS. She also has first-hand knowledge of the frustrations and anxiety surrounding the disease, as she had MS for at least 15 years before receiving a diagnosis in 2003 and has had several relapses since her diagnosis.